tbuckley/cabot-search huggingface dataset:
Costs of Prescription Drugs for Children and Parental Adherence to Long-Term Medications
Authors: Julie C. Lauffenburger, Renee A. Barlev, Eniola Olatunji, Gregory Brill, Niteesh K. Choudhry
Journal: JAMA Network Open (2023)

The adverse effects of prescription drug costs on medication adherence and health have been well described for individuals. Because many families share financial resources, high medication costs for one could lead to cost-related nonadherence in another; however, these family-level spillover effects have not been explored.To evaluate whether the cost of a child's newly initiated medication was associated with changes in their parent's adherence to their own medications and whether that differed by likely duration of treatment.This cohort study used interrupted time-series analysis with a propensity score-matched control group from a large national US health insurer database (2010-2020) and included children initiating medication and their linked presumed parents using long-term medications.The cost of the child's initiated medication. Child medication cost was classified based on highest (≥90th) or lowest (<10th) decile from out-of-pocket medication spending, stratified by whether the medication was intended for short- or long-term use. Children initiating high-cost medications (based on the highest decile) were propensity-score matched with children initiating low-cost medications.The child's parent's adherence to long-term medication assessed by the widely used proportion of days covered metric in 30-day increments before and after the child's first fill date. Parent demographic characteristics, baseline adherence, and length of treatment, and family unit size and out-of-pocket medication spending were key subgroups.Across 47 154 included pairs, the parents' mean (SD) age was 42.8 (7.7) years. Compared with a low-cost medication, initiating a high-cost, long-term medication was associated with an immediate 1.9% (95% CI, -3.8% to -0.9%) reduction in parental adherence sustained over time (0.2%; 95% CI, -0.1% to 0.4%). Similar results were observed for short-term medications (0.6% immediate change; 95% CI, -1.3% to -0.01%). Previously adherent parents, parents using treatment for longer periods, and families who spent more out-of-pocket on medications were more sensitive to high costs, with immediate adherence reductions of 2.8% (95% CI, -4.9% to -0.6%), 2.7% (95% CI, -4.7% to -0.7%), and -3.8% (95% CI, -7.2% to -0.5%), respectively, after long-term medication initiation.In this cohort study small reductions in adherence across parents with higher child drug costs were observed. Health care systems should consider child-level or even household-level spending in adherence interventions or prescription policy design.
Lotilaner Ophthalmic Solution 0.25%: First Approval
Authors: Yahiya Y. Syed
Journal: Drugs (2023)

Lotilaner ophthalmic solution 0.25% (XDEMVY™), a gamma-aminobutyric acid-gated chloride channel (GABA-Cl) inhibitor selective for mites, is being developed by Tarsus Pharmaceuticals for the treatment of Demodex blepharitis and meibomian gland dysfunction in patients with Demodex lid infestation (Demodex-induced meibomianitis). On 24 July 2023, lotilaner ophthalmic solution 0.25% received its first approval in the USA for the treatment of Demodex blepharitis. The agent is also currently in phase 3 development for Demodex blepharitis in China and phase 2 development for Demodex-induced meibomianitis in the USA. This article summarizes the milestones in the development of lotilaner ophthalmic solution 0.25% leading to this first approval for the treatment of Demodex blepharitis in the USA.
State of the Art and Current Challenges on Electroactive Biomaterials and Strategies for Neural Tissue Regeneration
Authors: Teresa Marques‐Almeida, Senentxu Lanceros‐Mendez, Clarisse Ribeiro
Journal: Advanced Healthcare Materials (2023)

The loss or failure of an organ/tissue stands as one of the healthcare system's most prevalent, devastating, and costly challenges. Strategies for neural tissue repair and regeneration have received significant attention due to their particularly strong impact on patients' well-being. Many research efforts are dedicated not only to control the disease symptoms but also to find solutions to repair the damaged tissues. Neural tissue engineering (TE) plays a key role in addressing this problem and significant efforts are being carried out to develop strategies for neural repair treatment. In the last years, active materials allowing to tune cell-materials interaction are being increasingly used, representing a recent paradigm in TE applications. Among the most important stimuli influencing cell behavior are the electrical and mechanical ones. In this way, materials with the ability to provide this kind of stimuli to the neural cells seem to be appropriate to support neural TE. In this scope, this review summarizes the different biomaterials types used for neural TE, highlighting the relevance of using active biomaterials and electrical stimulation. Furthermore, this review provides not only a compilation of the most relevant studies and results but also strategies for novel and more biomimetic approaches for neural TE.
Can Preoperative Radiological Identification of Lung Tumor Invasiveness Be Improved?
Authors: Michael Kuan-Yew Hsin, David Chi-Leung Lam
Journal: JAMA Network Open (2023)

Ting Ye, MD; Haoxuan Wu, MD; Shengping Wang, MD; Qiao Li, MD; Yajia Gu, MD; Junjie Ma, MD; Jihong Lin, MD; Mingqiang Kang, MD; Bin Qian, MD; Hong Hu, MD; Yang Zhang, MD; Yihua Sun, MD; Yawei Zhang, MD; Jiaqing Xiang, MD; Yuan Li, MD; Xuxia Shen, MD; Zezhou Wang, PhD; Haiquan Chen, MD, PhD
Incorrect Data in Results and Figures
Journal: JAMA Network Open (2023)

Geoffrey C. Cloud, MB, BS; Jeff D. Williamson, MD; Le Thi Phuong Thao, PhD; Cammie Tran, MPH; Charles B. Eaton, MD; Rory Wolfe, PhD; Mark R. Nelson, PhD; Christopher M. Reid, PhD; Anne B. Newman, MD; Jessica Lockery, PhD; Sharyn M. Fitzgerald, PhD; Anne M. Murray, MD; Raj C. Shah, MD; Robyn L. Woods, PhD; Geoffrey A. Donnan, MD; John J. McNeil, PhD
Effectiveness of Monovalent mRNA Vaccines Against Omicron XBB Infection in Singaporean Children Younger Than 5 Years
Authors: Liang En Wee, Nicole Tang, Deanette Pang, Calvin Chiew, Chee-Fu Yung, Chia Yin Chong, Vernon Lee, Benjamin Ong, David Chien Lye, Kelvin Bryan Tan
Journal: JAMA Pediatrics (2023)

Literature on vaccine effectiveness of SARS-CoV-2 messenger RNA (mRNA) vaccines for children younger than 5 years is limited.
Intensive Lifestyle Intervention for Remission of Early Type 2 Diabetes in Primary Care in Australia: DiRECT-Aus
Authors: Samantha L. Hocking, Tania P. Markovic, Crystal M.Y. Lee, Tegan J. Picone, Kate E. Gudorf, Stephen Colagiuri
Journal: Diabetes Care (2023)

We aimed to assess whether remission of type 2 diabetes (T2D) could be achieved with a low-energy total diet replacement (TDR) in an Australian primary care setting.Individuals aged 20-65 years with T2D duration up to 6 years, BMI >27.0 kg/m2, and not treated with insulin were prescribed a 13-week low-energy TDR (Optifast; Nestlé Health Science) followed by 8-week structured food reintroduction and 31-week supported weight maintenance. The primary outcome was T2D remission at 12 months.A total of 155 participants comprised the intention-to-treat population. At 12 months, T2D remission was achieved in 86 (56%) participants, with a mean adjusted weight loss of 8.1% (95% CI 7.2-9.1). Two serious adverse events requiring hospitalization related to the study intervention were reported.At 12 months T2D remission was achieved for one in two Australian adults in a primary care setting.
Silicon‐Based Biomaterials Modulate the Adaptive Immune Response of T Lymphocytes to Promote Osteogenesis/Angiogenesis via Epigenetic Regulation
Authors: Lunguo Xia, Tingting Wu, Lei Chen, Peng Mei, Lu Liu, Ruomei Li, Mengmeng Shu, Zhiguang Huan, Chengtie Wu, Bing Fang
Journal: Advanced Healthcare Materials (2023)

Abstract Silicon (Si)‐based biomaterials are widely applied for bone regeneration. However, the underlying mechanisms of the materials function remain largely unknown. T lymphocyte‐mediated adaptive immune response plays a vital role in the process of bone regeneration. In the current study, mesoporous silica (MS) is used as a model material of Si‐based biomaterials. It shows that the supernatant of CD4 + T lymphocytes pretreated with MS extract significantly promotes the vascularized bone regeneration. The potential mechanism is closely related to the fact that MS extract can reduce the expression of regulatory factor X‐1 (RFX‐1) in CD4 + T lymphocytes. This may result in the overexpression of interleukin‐17A (IL‐17A) by boosting histone H3 acetylation and lowering DNA methylation and H3K9 trimethylation. Importantly, the in vivo experiments further reveal that MS particles significantly enhance bone regeneration with improved angiogenesis in the critical‐sized calvarial defect mouse model accompanied by upregulation of IL‐17A in peripheral blood and the proportion of Th17 cells. This study suggests that modulation of the adaptive immune response of T lymphocytes by silicate‐based biomaterials plays an important role for bone regeneration.
Mitochondrial dysfunction-associated microbiota establishes a transmissible refractory response to anti-TNF therapy during ulcerative colitis
Authors: Ainize Peña-Cearra, Janire Castelo, Jose Luis Lavín, Monika Gonzalez-Lopez, Miguel Angel Pascual-Itoiz, Miguel Fuertes, Virginia Gutiérrez de Juan, Laura Bárcena, Itziar Martín-Ruiz, Aize Pellón, Iratxe Seoane, Diego Barriales, Ainhoa Palacios, Asier Fullaondo, Iago Rodríguez-Lago, María L. Martinez-Chantar, Ana Mª Aransay, Hector Rodriguez, Juan Anguita, Leticia Abecia
Journal: Gut Microbes (2023)

Anti-TNF therapy can induce and maintain a remission status during intestinal bowel disease. However, up to 30% of patients do not respond to this therapy by mechanisms that are unknown. Here, we show that the absence of MCJ, a natural inhibitor of the respiratory chain Complex I, induces gut microbiota changes that are critical determinants of the lack of response in a murine model of DSS-induced inflammation. First, we found that MCJ expression is restricted to macrophages in human colonic tissue. Therefore, we demonstrate by transcriptomic analysis of colon macrophages from DSS-induced mice that MCJ-deficiency is linked to the expression of genes belonging to the FcγR signaling pathway and contains an anti-TNF refractory gene signature identified in ulcerative colitis patients. The gut microbial composition changes observed upon DSS treatment in the MCJ-deficient mice revealed the increased presence of specific colitogenic members, including Ruminococcus gnavus and Oscillospira, which could be associated with the non-response to TNF inhibitors. Further, we show that the presence of a microbiota associated resistance to treatment is dominant and transmissible to responsive individuals. Collectively, our findings underscore the critical role played by macrophage mitochondrial function in the gut ecological niche that can substantially affect not only the severity of inflammation but also the ability to successfully respond to current therapies.
Introducing the Guide to Statistics and Methods
Authors: Heather Gwynn Allore, Yorghos Tripodis, Sharon K. Inouye
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Industry Payments Received by Residents During Training
Authors: Sean O. Hogan, Kenji Yamazaki, Yuezhou Jing, Bruce J. Trock, Misop Han, Eric Holmboe
Journal: JAMA Network Open (2023)

Those responsible for medical education-specialties, sponsoring institutions, and program directors (PD)-are independently associated with the professional identity formation of the trainees with respect to potential conflicts of interest.To identify the relative degree to which factors in the training environment are associated with resident acceptance of payments from pharmaceutical and medical device companies.Cross-sectional, retrospective study of residents enrolled in the 3 largest primary-care specialties (internal medicine [IM], family medicine [FM], obstetrics and gynecology [OBGYN]) and 3 largest surgical disciplines (general surgery [GS], orthopedic surgery, and urology) during academic year 2020 to 2021. All analyses were conducted January through August 2023.Specialty, sponsoring institutions' ownership (nonprofit, for-profit, federal government, local government, or state government), and the number of payments PDs accepted.Modified Poisson regression assessed the relative risk of ownership, specialty, and PD behavior on residents' acceptance of industry payments as recorded in the Open Payments Program (OPP) database.In total, there were 124 715 residents in all training programs during 2020 to 2021, 12% of whom received payments totaling $6.4 million. There were 65 992 residents in training during 2020 to 2021 in the 6 specialties evaluated in this study, with 4438 in orthopedics, 1779 in urology, 9177 in GS, 5819 in OBGYN, 14 493 in FM, and 30 286 in IM. OPP records $3.9 million in payments to the 8750 residents (13.4%) who received at least 1 industry payment. The record of all payments to residents in OPP totals $6.4 million. Compared with residents in federal sponsoring institutions, those affiliated with for-profit institutions were 3.50 (95% CI, 2.32-5.28) times more likely to accept industry payments, while those affiliated with nonprofit organizations were 2.00 (95% CI, 1.36-2.93) times more likely to accept payments. Compared with IM, residents in each of the following specialties have an elevated risk of accepting payments: orthopedics, 3.21 (95% CI, 2.73-3.77) times; urology, 2.95 (95% CI, 2.44-3.56) times; GS, 1.21 (95% CI, 1.00-1.45) times; OBGYN, 1.30 (95% CI, 1.05-1.62) times. The difference in the risk of accepting a payment between FM and IM residents was not statistically significant. The number of payments PDs accepted slightly elevated the risk of residents to accept a payment by 1.01 (95% CI, 1.01-1.01).In this cross-sectional, retrospective study, receipt of industry payments by residents was associated with specialty, institutional control, and PD behavior.
Patterns of Social Determinants of Health and Child Mental Health, Cognition, and Physical Health
Authors: Yunyu Xiao, J. John Mann, Julian Chun-Chung Chow, Timothy T. Brown, Lonnie R. Snowden, Paul Siu-Fai Yip, Alexander C. Tsai, Yu Hou, Jyotishman Pathak, Fei Wang, Chang Su
Journal: JAMA Pediatrics (2023)

Importance Social determinants of health (SDOH) influence child health. However, most previous studies have used individual, small-set, or cherry-picked SDOH variables without examining unbiased computed SDOH patterns from high-dimensional SDOH factors to investigate associations with child mental health, cognition, and physical health. Objective To identify SDOH patterns and estimate their associations with children’s mental, cognitive, and physical developmental outcomes. Design, Setting, and Participants This population-based cohort study included children aged 9 to 10 years at baseline and their caregivers enrolled in the Adolescent Brain Cognitive Development (ABCD) Study between 2016 and 2021. The ABCD Study includes 21 sites across 17 states. Exposures Eighty-four neighborhood-level, geocoded variables spanning 7 domains of SDOH, including bias, education, physical and health infrastructure, natural environment, socioeconomic status, social context, and crime and drugs, were studied. Hierarchical agglomerative clustering was used to identify SDOH patterns. Main Outcomes and Measures Associations of SDOH and child mental health (internalizing and externalizing behaviors) and suicidal behaviors, cognitive function (performance, reading skills), and physical health (body mass index, exercise, sleep disorder) were estimated using mixed-effects linear and logistic regression models. Results Among 10 504 children (baseline median [SD] age, 9.9 [0.6] years; 5510 boys [52.5%] and 4994 girls [47.5%]; 229 Asian [2.2%], 1468 Black [14.0%], 2128 Hispanic [20.3%], 5565 White [53.0%], and 1108 multiracial [10.5%]), 4 SDOH patterns were identified: pattern 1, affluence (4078 children [38.8%]); pattern 2, high-stigma environment (2661 children [25.3%]); pattern 3, high socioeconomic deprivation (2653 children [25.3%]); and pattern 4, high crime and drug sales, low education, and high population density (1112 children [10.6%]). The SDOH patterns were distinctly associated with child health outcomes. Children exposed to socioeconomic deprivation (SDOH pattern 3) showed the worst health profiles, manifesting more internalizing (β = 0.75; 95% CI, 0.14-1.37) and externalizing (β = 1.43; 95% CI, 0.83-2.02) mental health problems, lower cognitive performance, and adverse physical health. Conclusions This study shows that an unbiased quantitative analysis of multidimensional SDOH can permit the determination of how SDOH patterns are associated with child developmental outcomes. Children exposed to socioeconomic deprivation showed the worst outcomes relative to other SDOH categories. These findings suggest the need to determine whether improvement in socioeconomic conditions can enhance child developmental outcomes.
Abnormal lactate metabolism is linked to albuminuria and kidney injury in diabetic nephropathy
Authors: Kengo Azushima, Jean-Paul Kovalik, Takahiro Yamaji, Jianhong Ching, Tze Wei Chng, Jing Guo, Jian-Jun Liu, Mien Nguyen, Rashidah Binte Sakban, Simi E. George, Puay Hoon Tan, Su Chi Lim, Susan B. Gurley, Thomas M. Coffman
Journal: Kidney International (2023)
Landscape of Clinical Resistance Mechanisms to FGFR Inhibitors in FGFR2-Altered Cholangiocarcinoma
Authors: Qibiao Wu, Haley Ellis, Giulia Siravegna, Alexa G. Michel, Bryanna L. Norden, Ferran Fece de la Cruz, Eranga Roshan Balasooriya, Yuanli Zhen, Vanessa S. Silveira, Jianwe Che, Ryan B. Corcoran, Nabeel Bardeesy
Journal: Clinical Cancer Research (2023)

FGFR inhibitors are effective in FGFR2-altered cholangiocarcinoma, leading to approval of reversible FGFR inhibitors, pemigatinib and infigratinib, and an irreversible inhibitor, futibatinib. However, acquired resistance develops, limiting clinical benefit. Some mechanisms of resistance have been reported, including secondary FGFR2 kinase domain mutations. Here, we sought to establish the landscape of acquired resistance to FGFR inhibition and to validate findings in model systems.
Quorum sensing modulates bacterial virulence and colonization dynamics of the gastrointestinal pathogen <i>Citrobacter rodentium</i>
Authors: Jorge Peña-Díaz, Sarah E. Woodward, Anna Creus-Cuadros, Antonio Serapio-Palacios, Stephanie Ortiz-Jiménez, Wanyin Deng, B. Brett Finlay
Journal: Gut Microbes (2023)

Quorum Sensing (QS) is a form of cell-to-cell communication that enables bacteria to modify behavior according to their population density. While QS has been proposed as a potential intervention against pathogen infection, QS-mediated communication within the mammalian digestive tract remains understudied. Using an LC-MS/MS approach, we discovered that Citrobacter rodentium, a natural murine pathogen used to model human infection by pathogenic Escherichia coli, utilizes the CroIR system to produce three QS-molecules. We then profiled their accumulation both in vitro and across different gastrointestinal sites over the course of infection. Importantly, we found that in the absence of QS capabilities the virulence of C. rodentium is enhanced. This highlights the role of QS as an effective mechanism to regulate virulence according to the pathogen's spatio-temporal context to optimize colonization and transmission success. These results also demonstrate that inhibiting QS may not always be an effective strategy for the control of virulence.
PM <sub>2.5</sub> induced neurotoxicity through unbalancing vitamin B12 metabolism by gut microbiota disturbance
Authors: Xuan Zhu, Yanting Xia, Huanhuan Wang, Lihua Shi, Hongping Yin, Meier Gu, Fujie Yan
Journal: Gut Microbes (2023)

Fine particulate matter (PM2.5) in the atmosphere is easily accompanied by toxic and harmful substances, causing serious harm to human health, including cognitive impairment. Vitamin B12 (VitB12) is an essential micronutrient that is synthesized by bacteria and contributes to neurotransmitter synthesis as a nutrition and signaling molecule. However, the relationship between VitB12 attenuation of cognitive impairment and intestinal microbiota regulation in PM2.5 exposure has not been elucidated. In this study, we demonstrated that PM2.5 caused behavioral defects and neuronal damage in Caenorhabditis elegans (C. elegans), along with significant gene expression changes in neurotransmitter receptors and a decrease in VitB12 content, causing behavioral defects and neuronal damage in C. elegans. Methylcobalamin (MeCbl), a VitB12 analog, alleviated PM2.5-induced neurotoxicity in C. elegans. Moreover, using in vivo and in vitro models, we discovered that long-term exposure to PM2.5 led to changes in the structure of the gut microbiota, resulting in an imbalance of the VitB12-associated metabolic pathway followed by cognitive impairment. MeCbl supplementation could increase the diversity of the bacteria, reduce harmful substance contents, and restore the concentration of short-chain fatty acids (SCFAs) and neurotransmitters to the level of the control group to some degree. Here, a new target to mitigate the harm caused by PM2.5 was discovered, supplying MeCbl for relieving intestinal and intracellular neurotransmitter disorders. Our results also provide a reference for the use of VitB12 to target the adjustment of the human intestinal microbiota to improve metabolic disorders in people exposed to PM2.5.
A New Framework for Dementia Nomenclature
Authors: Ronald C. Petersen, Sandra Weintraub, Marwan Sabbagh, Jason Karlawish, Charles H. Adler, Peggye Dilworth-Anderson, Lori Frank, Cynthia Huling Hummel, Angela Taylor
Journal: JAMA Neurology (2023)

Nomenclature in the field of neurodegenerative diseases presents a challenging problem. Inconsistent use of terms such as Alzheimer disease and dementia has compromised progress in clinical care, research, and development of therapeutics. Dementia-associated stigma further contributes to inconsistent and imprecise language. The result is a lack of clarity that produces confusion with patients and the general public and presents communication challenges among researchers. Therefore, the Advisory Council on Research, Care, and Services of the National Plan to Address Alzheimer's Disease authorized a committee to make recommendations for improvement.